Recovery of Male Reproductive Function After Ceasing Prolonged Testosterone Undecanoate Injections

Context: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known. Objective: To investigate rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections. Methods: Men (n=303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo(P)-controlled randomized clinical trial of TU treatment were recruited for a further 12 months while remaining blinded to treatment. Sex steroids (T, DHT, E2, E1) by LCMS, LH, FSH and SHBG by immunoassays and sexual function questionnaires (Psychosexual Diary Questionnaire (PDQ), International Index of Erectile Function (IIEF), SF-12) were measured at entry (three months after last injection) and 6, 12, 18, 24, 40 and 52 weeks later. Results: In the nested cohort of TU-treated men, serum T was initially higher but declined to 12 weeks remaining stable thereafter with serum T and SHBG 11% and 13%, respectively, lower than P-treated men. Similarly, both questionnaires showed initial carryover higher scores in T-treated men, but after weeks 18 showed no difference between T and P treated men. Initially fully suppressed serum LH and FSH recovered slowly towards the participant’s own pre-treatment baseline over 12 months since last injection. Conclusions: After stopping 2 years of 1000 mg injectable TU treatment, full reproductive hormone recovery is slow and progressive over 15 months since last testosterone injection but may take longer than 12 months to be complete. Persistent proportionate reduction in serum SHBG and T reflects lasting exogenous T effects on hepatic SHBG secretion rather than androgen deficiency.

Correlation Between Nongenomic Action of C19-Steroids and COVID-19 Severity

The recent COVID-19 pandemic is the defining global health crisis of our time and little is known about this disease. It has been reported that advanced age is considered a major risk factor for COVID-19 complications, and data suggest that this disease is deadlier for men than women but these observations are currently unclear. Regarding androgen action, it has been shown that certain smooth muscles are a target for androgens by inducing an acute relaxing effect in airway and vascular tissues that is nongenomically mediated; likewise, androgens are capable of inducing genomic anti-inflammatory and nongenomic hypotensive responses. The aim of this report is to associate the relationship between COVID-19 and aging men as well as the comorbidities presented in this group of patients linked with androgen deficiency. Remarkably, the nongenomic mechanisms of androgens as potential protectors are reviewed. On this basis, it is suggested that hypotestosteronemia may be a risk factor for COVID-19 severity.

Relationship between indicators of insulin resistance and oxidative balancein adolescents with androgen deficiency

The purpose of the work was to study the relationship between the indicators of insulin resistance (IR), free radical oxidation products (FRO) levels, and the antioxidant system activity in adolescents with androgen deficiency (AD).Materials and methods. 58 adolescents 13­—18 years old with AD were examined. Serum levels of total testosterone, glucose, insulin, tiobarbituric acid active compounds (TBA), carbonylated proteins (CB), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity were determined. The HOMA index and the coefficient of oxidative stress were calculated.Results and discussion. In the group of adolescents with AD without IR, an inverse correlation was found between the HOMA index and CAT activity. CAT activity negatively correlated with CB content and glucose concentration. In addition, an inverse relationship was found between the activity of GPO and SOD. IR indices indirectly, through feedback with the activity of CAT, influence to the formation of conditions for inhibition/activation of FRO of proteins.IR was revealed in 37.9 % of the examined adolescents with AD. Direct relationship was recorded between IR indicators and markers of oxidative stress, as well as between testosterone levels and GPx activity in the group of these patients. Direct correlation between the coefficient of oxidative stress and the content of TBA-­active compounds indicates the formation of oxidative stress due to the activation of lipid peroxidation. Reduced testosterone levels in adolescents with AD inhibits an increase in GPx activity and prevents compensation for excessive intensity of free radical processes. Conclusion. The results indicate that adolescents with AD have a close relationship between the processes of carbohydrate metabolism, FRO, and antioxidant protection.In adolescents with AD without IR, a balancebetween the studied parameterswas found.The formation of IR in adolescents with AD shifts the equilibrium of the oxidative balance towards the activation of FRO processes. Decreased testosterone levels in adolescents with AD do not maintain the body’s antioxidant status within normal limits.

Correction of Androgen Deficiency in Men with Type 2 Diabetes

Background: In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. Aim: to investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Materials and methods: Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. Results: The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). Conclusion: The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.

Prevalence of androgen deficiency in aging male in an outpatient population and effects of testosterone gel reposition therapy

Background: Androgen deficiency in aging male (ADAM) is characterized by hypogonadism with symptoms such as reduced sexual desire, muscle mass loss, among others. The treatment with testosterone gel and the results around weight and other indicators are the research objects. Objective: Analysis of association between ADAM and obesity in the outpatient population studied and to verify the outcomes of the testosterone gel treatment. Materials & Methods: From a group of 126 outpatients of University Hospital Mário Palmério, 40 were selected with total testosterone lower than 300ng/dL, upon the signature of written informed consent form and the realization of laboratory tests. After new testosterone dosage and urologic evaluation, 6 patients were treated for an average time of 6 months. Initially the dosage was 50 mg/day, with medical consultations and laboratory tests to verify the effects and to adjust the dosage. The variables analyzed were BMI, abdominal circumference, weight, muscle mass, body and visceral fat, in addition to testosterone serum dosages, lipid profile, amongst others, considering the test t among the beginning and end of treatment, defining the significance level by p<0,05. Results: Significant increase of total testosterone levels (p<0,001) and a tendency of improvement in the free testosterone levels (p=0,061) and no significant reduction of BMI (p=0,4308), abdominal circumference (p=0,1695), weight (p=0,999), body fat (p=0,194) and muscle mass (p=0,632), while visceral fat increased (p=0,5265). Vitamin D had no significant increase (p=0,2422). Conclusion: The total testosterone level was increased after the testosterone gel treatment with statistical significance, however there must be new research with more subjects with ADAM to prove the benefits of this treatment.

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

Background To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls. Methods We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression. Results The questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression. Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p < 0.001; cluster headache 5.62 ± 0.99, p < 0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p < 0.001; cluster headache: − 5.25 ± 0.56, p < 0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001). Conclusion Men with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.

Influence of androgen deficiency on the endometrium structure in women of reproductive age

Aim — to identify the relationship between androgen deficiency and the development of endometrial hypoplasia in women of reproductive age, to develop an algorithm for the diagnosis and treatment of this category of women. Materials and methods. Examination of patients with androgen deficiency revealed 48 patients with endometrial hypoplasia based on the ultrasound markers. After examination for CD138 and detection of chronic endometritis during the study, 9 patients were excluded. At the second stage, an immunohistochemical examination was performed for the expression of receptors for estrogen, progesterone and androgens. According to the results, the patients were divided into 2 groups: the first group (24 patients) with a high level of expression of androgen receptors and the second group (15 patients) with a low level of expression of androgen receptors. Theexpressionof receptors to estrogens and progesterone was on medium level and comparative in both groups. Both groups of patients underwent hormonal therapy for 3 months: estradiol valerate 1 g per day in a continuous mode and 200 mg of micronized progesterone from the sixteenth to twenty-fifth days of the menstrual cycle. Additionally, patients of the first group received dehydro­epian­drosterone(DHEA)in a dose of 25 mg per day continuously in the form sublingual spray. Results. According to the data of ultrasound examination in the first group of patients, the endometrium corresponded to normal parameters both during treatment and 1 and 3 months after stopping treatment. At the same time, in the second group of patients, there was an improvement in the thickness (more than 7 mm) and structure of the endometrium during treatment and the absence of these effects after the termination of hormonal therapy. Considering the recommendations of the Association of Endocrinologists on the superiority of non-tablet forms of androgen preparations in the treatment of androgen deficiency and having a positive and long-term effect when taking sublingual DHEA, it is possible to recommend adding the above form of DHEA to systemic therapy of endometrial hypoplasia against the background of androgen deficiency. Conclusions. Women with androgen deficiency are more likely to have concomitant endometrial hypoplasia. Immunohistochemical examination of the endometrium of women of reproductive age with androgen deficiency in 24 patients (61.5 %) revealed a high level of expression of androgen receptors. The effectiveness of therapy for endometrial hypoplasia in women with androgen deficiency with addition of androgens to the standard regimens is more effective and has a long-lasting effect. The combination of estrogen-gestagenic therapy and androgens has a positive effect on the gestational potential of the endometrium in women of reproductive age with androgen deficiency.

Influence of testosterone on purine metabolism and gout

Many different factors are involved in the regulation of purine metabolism. An important role is played by the level of sex hormones: high concentrations of androgens lead to a higher, and estrogen – to a lower level of uric acid. However, according to the results of numerous studies, it has been shown that the effect of sex hormones is not limited only to the uric acid concentration. Sex hormones affect inflammatory processes in the body by modulating the production of pro-inflammatory cytokines and regulating the corresponding signaling pathways. Androgen deficiency can lead to obesity and metabolic disorders, which can contribute to the development and course of gout. This review examines the effect of testosterone, as well as the effect of changes in its concentration on the dynamics of purine metabolism and gout.